Dirofilaria immitis

Dirofilaria immitus - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine

Dirofilariasis. Courtesy of T. Scase

Dirofilaria immitus - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine

Dirofilaria immitis:

a filarial worm
females: up to 30cm long; males: up to 15cm long
life-span 5-7years
up to 250 worms may establish in the heart and pulmonary arteries
produce microfilariae, not eggs.
May cause muscle ischaemia in dogs due to arteritis and thrombosis of external iliac arteries and their branches
Dirofilaria immitis live in heart and pulmonary arteries of dogs and cats

Microfilariae:

in peripheral circualtion
periodicity - maximum numbers in blood evening/night
greater than 300µm long
life-span 2years
present in approximately 60% of infected dogs
microfilariae are absent from the circulating blood if:
- only immature worms present
- only one worm present
- only one sex
- microfilariae killed by immune response (in 15% of dogs)
- females sterilised by chemotherapy (e.g. ivermectin).

Intermediate hosts:

many, but not all, species of mosquito.

Local Epidemiology:

determined by feeding preferences of local species, and population density.
up to 45% of non-protected dogs infected in some parts of USA.

In mosquito:

microfilariae → L1 → L2 → infective L3
this takes 1week at 30°C, or 4weeks at 18°C - there is no development below 14°C.
when mosquito next feeds:
- L3 moves to mouthparts
- up to 12 L3 deposited on skin
- enter body via puncture wound.

Zoonotic hazard:

human infection can occur, but few cases are diagnosed
this usually happens when a radio-opaque plaque is detected in the lung, and further investigation shows it to be caused by a trapped D. immitis larva.

Pathology

Worms produce:

substances that are:
- antigenic
- immunomodulatory
- pharmacologically active.

Lesions are:

not confined to the location of the worms
also caused by shear stress of high blood flow.

Severity:

not associated with the number of worms
exacerbated by exercise (i.e. by high blood flow rate)
sedentary dogs often asymptomatic - symptoms most commonly associated with racing greyhounds.

Acute prepatent disease:

immature adult worms in caudal distal pulmonary arteries
leads to intense diffuse eosinophilic reaction, which in turn leads to coughing.

Chronic disease:

mature worms in right heart and pulmonary arteries
endothelial swelling and sloughing
increased permeability → inflammation → periarteritis
platelets/white blood cells activated → thrombosis
proliferation of smooth muscle, thickening of media:

→ impairment of blood flow

→ pulmonary hypertension

→ right ventricular strain

→ right ventricular hypertrophy and right-sided heart failure

insufficient blood pumped through pulmonary capillary bed → insufficient preload for left ventricle.

Post Caval Syndrome (Dirofilarial haemoglobinuria):

can be acute or chronic
heavy heartworm infestation:
- entangled clumps of worms → impaired closure of tricuspid valve → post-caval stagnation → hepatic congestion and hepatic failure
this is accompanied by increased red blood cell fragility, haemolytic anaemia and haemolobinuria.

Clinical signs:

often sudden onset severe lethargy and weakness, but:
signs variable, reflecting multiple system dysfunction - pulmonary circulation, heart, liver and kidneys:
- lung damage (severe pulmonary hypertension; thromboembolism)
- heart failure (right-sided congestive)
therefore, not pathognomonic
acute prepatent = coughing
chronic = exercise intolerance, sometimes with ascites
acute post caval syndrome = collapse (dyspnoea, pale mucous membranes or jaundice, haemoglobinuria)

Diagnosis:

Physical examination:
- signs of heart disease
- lung involvement
Radiography:
- enlargement of right heart, main pulmonary arteries; arteries in lung lobes with thickening and tortuosity; inflammation in surrounding tissues
ECG:
- right axis deviation → deep S waves
Echocardiography:
- if post caval syndrome suspected - right ventricular enlargement with worms in ventricle appearing as parallel lines.

Clinical pathology:

needed alongside physical examination and other tests to determine treatment strategy and prognosis.

Parasite detection:

methods for demonstrating microfilariae in blood:
- wet blood smear (okay for quick look, but insensitive) = D. immitis not progressively motile
- Knott's test = red blood cells lysed; stained sediment examined
- micropore filter = blood forced through; microfilariae held on filter; stained and examined
- antibody detection ELISA = not reliable in dogs, but it is the best for cats (although some false positives)
- antigen detection ELISA (using specific antigen from adult female worm) = reliable positives from 5-7months post-infection in dogs; although occasional false negatives occur → not useful for cats
the immunochromatographic test (ICT) uses coloured gold colloidal particles tagged to monoclonal antibodies to visualise the presence of adult worm antigen - performance similar to antigen detection ELISA, but quicker and easier to do (but not as quantitative as some ELISAs are)
operator error can give false positives, therefore best to confirm result with another test.

Chemotherapy:

three treatment objectives needing different approaches:

1) Adulticidal

risk that dead worms → thromboembolism → respiratory failure
therefore, hospitalise and strict exercise restriction for at least 3weeks post-treatment
organic arsenicals for adulticidal therapy:
- Thiacetarsamide (2.2mg/kg IV bid for 2days) - hepatotoxic; skin sloughing
- Melarsomine (2.5mg/kg IM sid for 2days) - generally safer, but greater risk of thromboembolism

NB - Ivermectin preventative doses over 16months reduces adult worm numbers

2) Microfilaricidal

start 3-6weeks after adulticidal therapy:
- Ivermectin (50µg/kg)
- Milbemycin oxime (0.5mg/kg)

NB - risk of reaction to dead microfilariae in sensitised animals (lethargy, retching, tachycardia, circulatory collapse) - observe for 8hours post-treatment

3) Preventative (prophylactic)

objective = kill migrating L4 before they reach the heart
monthly treatments are 100% effective and safe if used properly, but often fail because of inadequate owner compliance
test for adult infection/microfilarie before start and annually thereafter:
- Ivermectin (6µg/kg monthly) - blocks maturation of larvae; these die only after several months
- Selamectin (6mg/kg monthly)
- Moxidectin (injectable formulation - 0.17mg/kg gives 6months protection)
- Milbemycin oxime (0.5mg/kg monthly) - care → kills microfilarie, therefore risk of reaction
- DEC (diethylcarbamazine) daily - care → kills microfilarie, therefore severe risk of reaction

Treatment of Post Caval Syndrome:

surgical removal with forceps via jugular vein
usually very successful, but:
do not crush or fragment worms

→ massive release of antigen

→ cardiac failure and acute respiratory distress

→ rapid death

A typical therapy protocol:

1) Pre-treatment evaluation

2) Adulticide: 4-6weeks restricted exercise

3) Microfilaricide: 3weeks after adulticide

4) Initiation of monthly preventative treatments

5) Check for microfilariae after 2weeks

6) Check for adults (ELISA) 4-6months after adulticide, and before start of each subsequent mosquito season.

Cat

A canine parasite - see under Dog Nematodes for life-cycle etc.
Cats are abnormal hosts, and so D. immitis is not very infective for cats.
Nevertheless, feline infection is common (up to 25%) in some heavily endemic areas.
But only small numbers of adult worms (1-3) establish.
The prepatent period is longer (approximately 8months) than in the dog.
Few, if any, microfilariae are produced (<20% of cases positive).
The life-span of the worm is shorter (2-3years).
However: one dead adult → acute pulmonary crisis (thromboembolism).

Feline Heartworm Disease

Lung pathology similar to dog, but little heart pathology.
Coughing starts 4-6months post-infection.
Antibody-detection ELISA used for diagnosis, but false positives occur (antigen ELISA cannot be used as antigen rarely expressed in cats).
There is no licensed adulticidal therapy, and treatment may be fatal for the cat as well as the worm.
Ivermectin or selamectin can be used for prevention.

Heart Worm

(Cardiology)

Description

Life cycle of dirofilaria immitis

Dogs, cats, and ferrets can be affected

Cats are more resistant to infection compared to dogs, but it only takes one or two worms to cause serious disease in cats.

Caval Syndrome is the result of extremely heavy worm burdens and is rarely seen.

Infection with heart worm can affect the following structures:

1. Pulmonary arteries

e.g. pulmonary thromboembolism of dead worms

2. Pulmonary parenchyma

e.g. allergic pneumonitis

3. Heart

e.g. pulmonary thromboembolism-->pulmonary hypertension-->increased right ventricular afterload-->right ventricular hypertrophy-->myocardial failure-->right heart failure

4. Liver

e.g. hepatic congestion from heart failure

5. Kidneys

e.g. antigen-antibody complexes lead to glomerulonephropathies

Distribution

Endemic in the United States (especially southeast); South America, Southeast Asia, Middle East, Australia, Japan, Southern Europe

Warm weather conditions that support the mosquito population contribute to heart worm disease

Transmission

Several types of mosquitoes are the intermediate host to the nematode worm D. imitis

Mosquitoes are infected with D. imitis when they bite an infected animal with circulating microfilaria (L1 stage)

Signalment

Genetics & Breed Predisposition: Large Breeds; Male>Female; 4-8 years old on average; Untreated with prophylactics

Cats: Outdoor cats; Male>Female; 3-6 years old on average; Untreated with prophylactics

Diagnosis

History & Clinical Signs

-Asymptomatic +/- (Acute Infections)

-Symptomatic +/- (Chronic Infection)

-Exercise Intolerance

-Haemoptysis

-Coughing

-Tachypnea

-Syncope

-Right Heart Failure +/-

-Vomiting (cats)

-CNS signs (cats)

-Collapse (cats)

-Sudden Death (cats)

Physical Exam

-Signs of right sided heart failure

-Crackles heard on auscultation

-Splitting of the S2 heart sound signifies pulmonary hypertension

Staging Heartworm Disease

Class	Description
Class 1	No physical or clinical signs
Class 2	Mild cough, Slight radiographic changes
Class 3	Cough, Exercise intolerance, Dyspnoea, Abnormal lung sounds, Enlarged pulmonary artery, Signs of right heart failure
Class 4	Caval Syndrome; Signs of right heart failure, Abnormal lung sounds, Abnormal heart sounds, Death

Laboratory Findings

Lab Tests

Heartworm Antigen Testing (dogs, cats)

-ELISA test kits test antigens associated with female D. immitis infections

-False negatives with male only infections (common in cats)

Direct Blood Smear (dogs)

-Detects microfilaria from a blood sample

-Only works if the infection is very severe

-Not used on cats because after 6-8 weeks of a heart worm infection the microfilaria disappear.

Modified Knott's Test or Filter Tests (dogs)

-These centrifugal concentration techniques detect small amounts of microfilaria from a direct blood smear

- (+) test indicates microfilaria production by adults

-(-) test indicates either no infection or an occult infection (immune system destroys L1)

-If negative test results, follow up with antigen test to rule out occult infections

-Not used on cats because after 6-8 weeks of a heart worm infection the microfilaria disappear.

Antibody Testing (dogs, cats)

-(+) test only indicates exposure to D. immitis

-(-) test rules out D. immitis infection (useful in cats)

Laboratory findings

Biochemistry: increased liver enzymes, azotemia, proteinuria, hypoalbuminemia

Haematology: eosinophilia, basophilia, thrombocytopenia, neutrophilia with left shift if the animal has a pulmonary thromboembolism, non-regenerative anaemia

Radiography

-Enlarged right heart

-Dilation of main pulmonary artery

-Enlarged peripheral branches of pulmonary arteries (especially diaphragmatic lobes)

Electrocardiography (ECG)

-Usually normal

-Right Ventricular Enlargement +/- (deep S waves)

-Right Atrial Enlargement +/- (tall P waves)

-Atrial arrhythmias +/-

Echocardiography

-Right heart enlargement

-Dilation of the main pulmonary artery

-Visualization of D. immitis if the infection is severe

Treatment

Currently there are few treatment options for cats infected with heart worm except surgical removal in severe cases or the controversal use of thiacetarsamide.

In dogs with allergic pneumonitis, give oral corticosteroids before starting heart worm treatment.

1. Adulticidal (kills worms slowly)

e.g. melarsomine dihydrochloride, Thiacetarsamide

-Give two doses 24 hours apart or perform a graded-kill protocol (1 dose into epaxial muscles; repeat 1-3 months later; repeat 24 later)

-Rest animal for up to six weeks after treatment to avoid a thromboemolism (major treatment risk)

(If thromboembolism develops treat with: prednisolone, heparin, and oxygen)

-Perform an antigen test 3-6 months after treatment to ensure adult worms have been killed

2. Microfilaricidal (kills microfilaria)

-Given about 4 weeks after adulticidal treatment

e.g. milbemycin, ivermectin

-Modified Knott's test should be performed 3 weeks after microfilaricide treatment. If it is positive repeat microfilaricidal protocol. If negative proceed to preventative treatment.

3. Prophylaxis

-Test animals for heart worm before administering preventative treatment

-Give dogs a supply of monthly macrocyclic lactones

e.g. ivermectin, milbemycin, selamectin, moxidectin

-All year coverage is usually the best way to ensure owner compliance

Prognosis

-Dependent on the stage at which heart worm has been diagnosed.

-Caval Syndrome has a 50% survival with surgical removal of the heart worms

Establish in heart and pulmonary arteries
Larvae migrate through connective tissue
Immature adults move to caudal distal pulmonary arteries causing diffuse eosinophilic reaction in lung parenchyma, then migrate back to right ventricle
May cause pulmonary thromboembolism

cat

As in dogs above
Not very infective in cats but one dead adult causes acute pulmonary crisis - thromboembolism

Nematodes of Dogs - CANINE HEARTWORM

Dirofilaria immitis is one of the most important causes of morbidity and mortality in dogs in many regions of the world that have a warm, humid climate, including parts of southern Europe, USA and Australia.
The presenting signs are usually those of heart failure, but sudden collapse may occur in heavily infected dogs.
The endemic zone for canine heartworm disease is spreading as people increasingly travel with their pets.
Strains of D. immitis are adapting to cooler climates.
It is not endemic in the UK, but more infected dogs are likely to be imported now that the quarantine regulations have been relaxed.
It has a very long prepatent period, so clinical signs may not appear for many months after importation.
Although primarily a canine parasite, cats and ferrets can become infected.
Owners taking their pets into endemic regions require advice on how the disease can be prevented.

In dog:

larvae migrate through connective tissues and moult twice
immature adults (L5) are 1-5cm long → caudal distal pulmonary arteries in 4months → diffuse eosinophilic reaction in lung parenchyma, then migrate back towards right ventricle
start producing microfilariae 6-7months post-infection.